Association of epidermal growth factor receptor (<i>EGFR</i>) gene mutations with <i>EGFR</i> amplification in advanced non‐small cell lung cancer

Morinaga, Ryotaro; Okamoto, Isamu; Fujita, Yoshihiko; Arao, Tokuzo; Sekijima, Masaru; Nishio, Kazuto; Ito, Hiroyuki; Fukuoka, Masahiro; Kadota, Jun Ichi; Nakagawa, Kazuhiko

doi:10.1111/j.1349-7006.2008.00962.x

Cited by 32 publications

(20 citation statements)

References 42 publications

(93 reference statements)

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“…Subsequent mutation analyses of B-RAF or EML4-ALK translocations will further reduce the percentage of cases with unreliable results, since these alterations are currently considered to be mutually exclusive with EGFR mutations [16]. Furthermore, ARMS or yet other experimental methods [17][18][19][20][21][22] with a putative higher sensitivity for the detection of EGFR mutations than Sanger sequencing may be used subsequently in such settings.…”

Section: Discussionmentioning

confidence: 95%

Optimized algorithm for Sanger sequencing-based EGFR mutation analyses in NSCLC biopsies

et al. 2012

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Pulmonary adenocarcinoma patients harboring EGFR mutations can benefit from tyrosine kinase inhibitor therapy. Reliable molecular analyses and precise pathological reporting of the EGFR mutational status are factors essential for patient treatment and outcome. More than 70 % of all EGFR mutation analyses are performed on non-small cell lung cancer (NSCLC) biopsies. However, biopsies may not be sufficient for mutation analysis due to low tumor content and admixture with non-neoplastic cells. To define the minimal concentration of tumor cells required for reliable EGFR mutational diagnostics by Sanger sequencing and to develop an algorithm for routine diagnostics on biopsy material, we determined total numbers of tumor and non-tumor cells, calculated the tumor cell concentration and serially diluted DNA from EGFR-mutated NSCLC by adding DNA of non-tumor cells from the same section. A counted tumor cell concentration of 30 %, which refers to a histologically estimated concentration of 40 %, is necessary for reliable detection of all mutations. Based on these data, we developed an algorithm for evidence-based EGFR mutation analysis by Sanger sequencing in biopsy specimens, which was subsequently applied to 461 diagnostic cases. Optimized diagnostic testing results in 80 % reliable EGFR mutation analyses of biopsy specimens, while in 20 % of cases re-biopsies had to be recommended.

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Section: Discussionmentioning

confidence: 95%

Optimized algorithm for Sanger sequencing-based EGFR mutation analyses in NSCLC biopsies

et al. 2012

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“…Multiple studies have established that EGFR mutations are more common in women than men, in patients who have never smoked tobacco than in patients who have smoked tobacco, and in East Asians than in other ethnic groups. 7,25–29 In contrast to EGFR -mutated lung cancer, ALK gene fusions do not show sharp differences in prevalence according to sex and ethnic origin, but do show a similar strong association with patients who have never smoked tobacco and younger age. 11,18,30,31 However, while these clinical characteristics may have value for population studies, they are insufficiently specific to be used to select individual patients for treatment with a targeted inhibitor.…”

Section: Section I: When Should Molecular Testing For Nsclc Be Performentioning

confidence: 98%

Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology

Lindeman

Cagle

Beasley³

et al. 2013

Journal of Thoracic Oncology

1,001

961

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Objective To establish evidence-based recommendations for the molecular analysis of lung cancers that are that are required to guide EGFR- and ALK-directed therapies, addressing which patients and samples should be tested, and when and how testing should be performed. Participants Three cochairs without conflicts of interest were selected, one from each of the 3 sponsoring professional societies: College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Writing and advisory panels were constituted from additional experts from these societies. Evidence Three unbiased literature searches of electronic databases were performed to capture articles published published from January 2004 through February 2012, yielding 1533 articles whose abstracts were screened to identify 521 pertinent articles that were then reviewed in detail for their relevance to the recommendations. Evidence was formally graded for each recommendation. Consensus Process Initial recommendations were formulated by the cochairs and panel members at a public meeting. Each guideline section was assigned to at least 2 panelists. Drafts were circulated to the writing panel (version 1), advisory panel (version 2), and the public (version 3) before submission (version 4). Conclusions The 37 guideline items address 14 subjects, including 15 recommendations (evidence grade A/B). The major recommendations are to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor, respectively, in all patients with advanced-stage adenocarcinoma, regardless of sex, race, smoking history, or other clinical risk factors, and to prioritize EGFR and ALK testing over other molecular predictive tests. As scientific discoveries and clinical practice outpace the completion of randomized clinical trials, evidence-based guidelines developed by expert practitioners are vital for communicating emerging clinical standards. Already, new treatments targeting genetic alterations in other, less common driver oncogenes are being evaluated in lung cancer, and testing for these may be addressed in future versions of these guidelines.

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“…Recent studies have reported that EGFR mutations occur early during multistage pathogenesis of NSCLC and precede amplification, but not necessarily high polysomy [37,40,41]. In addition, Morinaga et al (2008) observed a specific association between mutations and amplification, underlying that EGFR amplification, but not high polysomy, correlates with mutations [42]. …”

Section: Discussionmentioning

confidence: 99%

Evaluation of 7q31 region improves the accuracy of EGFR FISH assay in non small cell lung cancer

Casorzo

Corigliano

Ferrero

et al. 2009

Diagnostic Pathology

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BackgroundIncrease of EGFR gene copy number consequent to gene amplification and/or polysomy of chromosome 7 has been significantly associated with better clinical outcome in Non Small Cell Lung Cancer (NSCLC) patients treated with Tyrosin-Kinase Inhibitors (TKIs).The primary method to detect EGFR copy number is FISH (Fluorescence in Situ Hybridization), that in lung cancer requires a precise standardization due to the presence of intratumor heterogeneity and high frequency of chromosome 7 polysomy.Recommendations and interpretative guidelines to discriminate NSCLC patients into FISH positive (gene amplification and high chromosome 7 polysomy) and FISH negative have been proposed by the University of Colorado Cancer Center (UCCC). However, in a subset of cases the distinction between EGFR amplification and chromosome 7 polysomy can be controversial because of a complex pattern of multiple EGFR and centromere signals.MethodsIn order to distinguish more accurately these two genetic events, 20 NSCLC FISH positive patients, showing a controversial pattern of EGFR and centromere specific signals, were further evaluated for the status of 7q31 distal region.ResultsA discrepancy between FISH results obtained with UCCC scoring system and 7q31 control was evidenced in 2 patients (10%).ConclusionOur data strengthen the usefulness of 7q31 region evaluation to discriminate EGFR amplification from chromosome 7 polysomy in controversial EGFR FISH positive cases. Since it has been reported a possible different contribution of amplification and polysomy to TKIs susceptibility in NSCLC, the clear distinction between these two genetic events may be important to identify a subset of patients more responsive to the therapy.

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Association of epidermal growth factor receptor (EGFR) gene mutations with EGFR amplification in advanced non‐small cell lung cancer

Cited by 32 publications

References 42 publications

Optimized algorithm for Sanger sequencing-based EGFR mutation analyses in NSCLC biopsies

Optimized algorithm for Sanger sequencing-based EGFR mutation analyses in NSCLC biopsies

Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology

Evaluation of 7q31 region improves the accuracy of EGFR FISH assay in non small cell lung cancer

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